The Francis Crick Institute
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Endosomal structure and APP biology are not altered in a preclinical mouse cellular model of Down syndrome

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journal contribution
posted on 2023-10-27, 10:25 authored by Claudia Cannavo, Karen Cleverley, Cheryl Maduro, Paige Mumford, Dale Moulding, Elizabeth MC Fisher, Frances K Wiseman
Individuals who have Down syndrome (trisomy 21) are at greatly increased risk of developing Alzheimer’s disease, characterised by the accumulation in the brain of amyloid-β plaques. Amyloid-β is a product of the processing of the amyloid precursor protein, encoded by the APP gene on chromosome 21. In Down syndrome the first site of amyloid-β accumulation is within endosomes, and changes to endosome biology occur early in Alzheimer’s disease. Here, we determine if primary mouse embryonic fibroblasts isolated from a mouse model of Down syndrome can be used to study endosome and APP cell biology. We report that in this cellular model, endosome number, size and APP processing are not altered, likely because APP is not dosage sensitive in the model, despite three copies of App.


Crick (Grant ID: 10194, Grant title: Tybulewicz FC001194)